Unsaturated dialkyl esters such as Compound (I) are conveniently prepared by Knoevenagel condensation of aldehydes (e.g., 2-Methyl-4-(2,6,6-trimethylcyclohex-1-en-1-yl)butanal, Compound III) with dialkyl malonates such as dimethyl or diethyl malonate.

The Knoevenagel condensation of aldehydes with dialkyl malonates is traditionally carried out in boiling toluene as solvent in presence of catalytically effective amounts of piperidinium acetate. Water formed in the reaction is continuously separated as an azeotrope. See G. Jones in “Organic Reactions” Vol. 15, J. Wiley, 1967). Long reaction times and low to moderate yields are obtained when these conditions are applied on Compound III. Under this conventional Knoevenagel condensation condition, the reaction suffers a long reaction time and a low yield.
Lehnert reported an improvement to the yield of the conventional Knoevenagel condensation by carrying out the condensation in presence of two equivalents of titanium tetrachloride and four equivalents of pyridine in tetrahydrofuran at 0-25° C. However, the reaction time was prolonged. See Lehnert et al., Tetrahedron Letters 54, 4723-24 (1970). Indeed, when Lehnert conditions were used to prepare the dialkyl ester
Compound I from the aldehyde Compound III, the reaction gave a yield of 81% with a reaction time of 18 hours at 25° C. See U.S. Pat. No. 8,765,980. In addition to the prolonged reaction time, the Lehnert improvement has another disadvantage, namely, the use of a large amount of titanium tetrachloride, an environmental and health hazard. Titanium tetrachloride explosively reacts with water, forming solid waste titanium dioxide and corrosive gas hydrogen chloride.
There is still a need for a green process for preparing unsaturated dialkyl esters with a high yield and a short reaction time, and without recourse to excessive amounts of corrosive and toxic chemical reagents.